The final objective of this effort is to construct and test a multivalent adenoviral vaccine candidate that elicits a potent immune response against Yersinia pestis, the causative agent of plague. The proposed work is a collaborative effort between the University of Texas Medical Branch (UTMB), Norwell, Inc., and Introgen Therapeutics, Inc. The plague vaccine project was selected in response to the growing concern surrounding the organism's use in a potential terrorism event. The NIAID, in response to this threat, has classified the organism as a Class A priority organism. Currently there are no commercially available vaccines for protection from plague in the instance of a bioterrorism event. The lack of a vaccine is particularly worrisome because of the pathogen's capability to inflict widespread morbidity and mortality, upon exposure, to both civilians and military personnel. Project Aims will focus on the development, production and evaluation of a vaccine candidate featuring the low calcium response (LcrV) antigen alone or in combination with two other protective Yersinia pestis antigens Caf1 (F1 capsular antigen) and YscF (a type 3 secretion system structural protein) in an adenoviral vector system. The adenoviral vector system was selected because it not only provides a viable delivery vehicle, but also because of the ability of the vector to elicit an immune response. Both mouse and guinea pig animal models proposed in this study are currently being used at the UTMB for inhalational anthrax and plague, and the aerobiology unit for infecting animals by the aerosol route is in place. We believe this program will provide a valuable first line of defense by deterrence for potential terrorists in search of weapons where no vaccine or treatment option exists. Further, the development of a multivalent adenoviral vaccine is not only significant for biodefense but also for combating global infectious disease. PUBLIC HEALTH RELEVANCE: The objective of this project is to construct and test a multivalent adenoviral vaccine candidate against Yersinia pestis (plague), a Class A priority organism. Currently there is no licensed vaccine for human use to protect against infection with plague despite the pathogen's capability to inflict widespread morbidity and mortality upon exposure to both civilians and military personnel.